Saturday, 27 December 2008

This is an article from NY Times that I edited a little for you since it was quite long. It speaks of very promising new genetic therapy using RNA for blocking or activating certain genes. While it obviously has many flaws to perfect, it looks like some drugs using RNA are getting to human trial tests which is a huge improvement. The only thing that bothers me is that the only way to bring that double-straned RNA into the cell is trough repressing the immune reaction of the body. And if that type of RNA is really viral, I cannot be suspicious toward the process. I simply don't approve when we try to put into our body something that is meant to stay out by removing its natural defences to the thing. Yeah, we're doing it with good purpose, but things often go wrong and the body should have a way to fight whatever we do to it. Ok, it might be little bit paranoid. I just think we shouldn't mess with out immune system in a weakening way, because it's very VERY useful.

The Promise and Power of RNA

The level of cholesterol in human body is controlled by the levels of a protein called PCSK9.

But a powerful new approach, called RNA interference, may help decreasing it. Instead of mopping up a protein after it has been produced, as a conventional drug would do, RNA interference turns off the faucet, halting production of a protein by silencing the gene that contains its recipe.

In monkeys, a single injection of a drug to induce RNA interference against PCSK9 lowered levels of bad cholesterol by about 60 percent, an effect that lasted up to three weeks. Alnylam Pharmaceuticals, the biotechnology company that developed the drug, hopes to begin testing it in people next year.

The drug is a practical application of scientific discoveries that are showing that RNA, once considered a mere messenger boy for DNA, actually helps to run the show. The classic, protein-making genes are still there on the double helix, but RNA seems to play a powerful role in how genes function.

RNA interference, or RNAi, discovered only about 10 years ago, is attracting huge interest for its seeming ability to knock out disease-causing genes. There are already at least six RNAi drugs being tested in people, for illnesses including cancer and an eye disease.

And while there are still huge challenges to surmount, that number could easily double in the coming year.

RNA and DNA are strands made up of the chemical units that represent the letters of the genetic code. Each letter pairs with only one other letter, its complement. So two strands can bind to each other if their sequences are complementary.

Genes, which contain the recipes for proteins, are made of DNA. When a protein is to be made, the genetic code for that protein is transcribed from the DNA onto a single strand of RNA, called messenger RNA, which carries the recipe to the cell’s protein-making machinery. Proteins then perform most functions of a cell, including activating other genes.

But scientists are now finding that a lot of DNA is transcribed into RNA without leading to protein production. Rather, the RNA itself appears to be playing a role in determining which genes are active and which proteins are produced.

Much attention has focused on micro-RNAs, which are short stretches of RNA, about 20 to 25 letters long. They interfere with messenger RNA, reducing protein production.

More than 400 micro-RNAs have been found in the human genome, and a single micro-RNA can regulate the activity of hundreds of genes, said David P. Bartel, a biologist at the Whitehead Institute in Cambridge, Mass., and at the Massachusetts Institute of Technology.

As a result, Dr. Bartel said, the activity of more than half the genes in the human genome is affected by micro-RNA.

Indeed, scientists have found that some micro-RNAs contribute to the formation of cancer and others help block it.

Other studies have found micro-RNAs important for the proper formation and functioning of the heart and blood cells.

Scientists are also finding other types of RNA, some of which may work differently from micro-RNA. By now, there are so many types of RNA that one needs a scorecard to keep track.

Besides micro-RNA (miRNA), the new ones include small interfering RNA (siRNA), piwi-interacting RNAs (piRNA), chimeric RNA, and promoter-associated and termini- associated long and short RNAs. They join an existing stable that included messenger RNA (mRNA), transfer RNA (tRNA), and small nucleolar RNA (snoRNA), which all play roles in protein production.

Scientists do not know what all the newly discovered RNA is doing. Some of it may be just a nonfunctional byproduct of other cellular processes.

And there is still uncertainty over how big a role RNA plays. Some scientists say proteins are like a light switch, turning genes on and off, while RNA usually does fine tuning, like a dimmer.

Despite the remaining mysteries, researchers and companies are moving rapidly to exploit the latest findings. While micro-RNAs are getting some attention, the biggest effort is on RNA interference.

RNA interference is induced when a short snippet of double-stranded RNA — called a small interfering RNA, or siRNA — enters a cell. The cell treats it much like a micro-RNA it might make on its own. That results in the silencing of a gene that corresponds to the inserted RNA.

Scientists believe that RNA interference evolved as a way to fight viruses, since double-stranded RNA is rare outside viruses.

Given that the sequences of genes are now known, it is fairly straightforward to synthesize a small interfering RNA that can serve as a drug to silence a gene. Still, there has not yet been a truly convincing demonstration that such drugs will work in people.

One risk is that the small RNA snippets might silence genes beyond the intended target. And that could mean that a drug based on these snippets would have unwanted side effects.

But the biggest challenge is getting the RNA into the cells where it is needed. Double-stranded RNA is rare outside viruses, so the cell is not likely to welcome it.

Chemical changes can be made to RNA to make it more stable and to avoid setting off the immune system. And the RNA can be inserted into little globules of fat or attached to polymers to help it get through the bloodstream and enter cells.

One shortcoming of RNA interference is that it can only turn genes off. But to treat some diseases, like those in which the body makes too little of a protein, it might be desirable to turn genes on or to increase their activity levels.

In one of the latest surprises in this field, scientists have found that RNA can do this too. They have discovered what they call RNA activation, or RNAa. The molecules that perform it are called either small activating RNAs (saRNA) or antigene RNAs (agRNA).source

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